Friction Mediates Scission of Tubular Membranes Scaffolded by BAR Proteins

Abstract

SummaryMembrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubular membranes. We demonstrate that the protein scaffold bound to the underlying tube creates a frictional barrier for lipid diffusion; tube elongation thus builds local membrane tension until the membrane undergoes scission through lysis. We call this mechanism friction-driven scission (FDS). In cells, motors pull tubes, particularly during endocytosis. Through reconstitution, we show that motors not only can pull out and extend protein-scaffolded tubes but also can cut them by FDS. FDS is generic, operating even in the absence of amphipathic helices in the BAR domain, and could in principle apply to any high-friction protein and membrane assembly.

Membrane scission driven by the PROPPIN Atg18

“…One model of autophagy therefore stipulates that Atg9-containing vesicles deliver lipids to the phagophore, probably by membrane fusion (Mari et al, 2010;Moreau et al, 2011;Orsi et al, 2012). Interesting examples are provided by the recent discoveries that simple crowding of proteins, or the frictional barrier to lipid diffusion that they create, can suffice to facilitate fission (Simunovic et al, 2017;Snead et al, 2017). Lack of Atg18 or WIPI protein activity might also rupture Atg9 cycling by stalling formation of Atg9 carriers at lipid donor membranes.…”

“…Additional mechanisms, by which Atg18 could promote fission, are the above-mentioned crowding and friction effects (Simunovic et al, 2017;Snead et al, 2017), but also lipid phase separation and the line tension resulting from it. Lipid phase separations can drive fission reactions, and they can be promoted or induced by proteins binding to one of the lipid phases.…”

Molecular mechanisms of force production in clathrin‐mediated endocytosis

“…Another major difference is that dynamin is required for membrane scission in mammals but is not required for CME in yeast . Because the precise molecular mechanism of membrane scission is not fully understood, it is possible that dynamin itself is not strictly required for CME in all organisms, especially since dynamin appeared quite late in evolution , and key aspects of its function could be performed instead by BAR domain proteins, the actin machinery, and other factors .…”

Resolution of macropinosomes, phagosomes and autolysosomes: Osmotically driven shrinkage enables tubulation and vesiculation

“…This explains why SNX dimers prefer to bind membranes with curvature mirroring that of their BAR domain, compared to flat membranes. Importantly, these considerations also imply that when a membrane is under tension, that is, when its k b is uncharacteristically high, assembly of BAR domain proteins and tubule formation will be strongly inhibited . The k b of an organellar membrane will be influenced by its lipid composition (eg, cholesterol strongly stiffens the membrane), but also by the prevailing osmotic gradient (eg, shruken vacuoles have a much lower bending modulus) .…”